Tomudex is a specific inhibitor of thymidylate synthease with clinical activity in colorectal cancer. We have demonstrated in vitro synergism between Tomudex (TOM) and IdUrd, a cytotoxic pyrimidine analog, against colon and bladder human carcinoma cell lines as well as increased IdUrd incorporation into DNA. We designed a phase I trial to determine the MTD, pharmacokinetics and biologic effects of escalating doses of the combination, with the IdUrd given as a 24 hour infusion after a TOM 15 minute infusion. Interim results were published in Proceedings of the American Association for Cancer Research, 39:321, 1998. This trial continues to be open for accrual. To date, 26 patients have been entered. It appears that we are nearing the maximal tolerated dose (MTD) for the first phase of the trial as one patient has experienced grade 4 neutropenia. Once the MTD is identified, the protocol will proceed to its second phase.